Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/6544
Título
Cardiomyocyte hypertrophy induced by Endonuclease G deficiency requires reactive oxygen radicals accumulation and is inhibitable by the micropeptide humanin
Autor(es)
Fecha de publicación
2018
Cita
Redox Biol. 2018; 16:146-156
Idioma
Inglés
Tipo de documento
journal article
Resumen
The endonuclease G gene (Endog), which codes for a mitochondrial nuclease, was identified as a determinant of cardiac hypertrophy. How ENDOG controls cardiomyocyte growth is still unknown. Thus, we aimed at finding the link between ENDOG activity and cardiomyocyte growth. Endog deficiency induced reactive oxygen species (ROS) accumulation and abnormal growth in neonatal rodent cardiomyocytes, altering the AKT-GSK3 beta and Class-II histone deacethylases (HDAC) signal transduction pathways. These effects were blocked by ROS scavengers. Lack of ENDOG reduced mitochondrial DNA (mtDNA) replication independently of ROS accumulation. Because mtDNA encodes several subunits of the mitochondrial electron transport chain, whose activity is an important source of cellular ROS, we investigated whether Endog deficiency compromised the expression and activity of the respiratory chain complexes but found no changes in these parameters nor in ATP content. MtDNA also codes for humanin, a micropeptide with possible metabolic functions. Nanomolar concentrations of synthetic humanin restored normal ROS levels and cell size in Endog-deficient cardiomyocytes. These results support the involvement of redox signaling in the control of cardiomyocyte growth by ENDOG and suggest a pathway relating mtDNA content to the regulation of cell growth probably involving humanin, which prevents reactive oxygen radicals accumulation and hypertrophy induced by Endog deficiency.
Palabras clave
Cardiac hypertrophy | ENDOG | Mitochondrial DNA | Humanin | MITOCHONDRIAL-DNA REPLICATION | MEF2 TRANSCRIPTION FACTOR | CARDIAC-HYPERTROPHY | OXIDATIVE STRESS | DEPENDENT ACTIVATION | TRANSLATION | ISCHEMIA | PATHWAY | DEATH | HDAC4
Versión en línea
DOI
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